Several laboratories have reported evidence for the existence of a postulated natriuretic hormone using both in vivo and in vitro bioassay systems. In support of this hypothesis, we have demonstrated that a toad bladder sodium transport inhibitor is present in plasma of dogs given large intravenous infusion of saline. Physiologic studies have suggested that this biologic activity could be some type of natriuretic hormone. This research proposal is aimed at further characterization of the toad bladder sodium transport inhibitory activity. Studies are proposed in normal dogs, and in dogs with partial ligation of the inferior vena cava and with aortic-caval fistulae to demonstrate possible "volume receptors" which might control release of the factor. The possible role of the factor in the normal regulation of the volume of extracellular fluid will be studied in man given excessive amounts of a mineralocorticoid or antidiuretic hormone. The clinical significance of the factor will be explored in studies of patients with generalized edema and in uremic patients. The chemical characteristics of the factor will be studied by liquid column chromatography. The effects of the factor on renal sodium excretion in rats will be studied. Finally, the mechanism of action of the inhibitor on toad bladder sodium transport will be studied by observing its interaction with various natriferic and antinatriferic agents.